The objectives of this research are to explore and define the role of reoxygenation and redistribution/recruitment in the response of primarily neoplastic cells to ionizing radiation. In order to ultimately increase the therapeutic ratio in the treatment of cancer, this project is designed to provide more definitive and comprehensive proof of these two phenomena, to explore and uncover the mechanisms responsible for them, and to find means by which they can be modified. The EMT6 tumor system in BALB/c mice will be used most extensively because of its capability for assay of clonogenic survival. Other mouse tumors that can be cloned in vitro will be sought and employed in analogous experiments wherever possible. The kinetics of reoxygenation will be investigated as it occurs after fractionated irradiation and after chemotherapy. The role of tumor cell motility as a cause of reoxygenation will be investigated using EMT6 multicell spheroids. Redistribution/recruitment will be studied by labeling EMT6 tumors in vivo and scoring labeling in colonies grown in vitro for 3-5 days. Double labeling (3HTdR/14CTdR) will be used to investigate flow after 125IUdR labeling. The relationship between the P and Q states with the degree of cell oxygenation and related variables will be studied on EMT6 tumor cells separated by velocity sedimentation.